A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year.

BACKGROUND: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation.

METHODS: Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study. Patient and graft survival, renal function, study drug dosing and discontinuations were evaluated at 1 year.

RESULTS: At 1 year, there was no difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft function (DGF) receiving MMF had significantly better graft survival (99% vs. 93%; P=0.01). Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus (98% vs. 91%; P=0.07). Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%; P=0.02).

CONCLUSIONS: Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF. Patient and graft survival were excellent in both arms. Renal function is superior for patients treated with tacrolimus + MMF combination.